Biowire Model of Interstitial and Focal Cardiac Fibrosis

Abstract

Myocardial fibrosis is a severe global health problem due to its prevalence in all forms of cardiac diseases and direct role in causing heart failure. The discovery of efficient antifibrotic compounds has been hampered due to the lack of a physiologically relevant disease model. Herein, we present a disease model of human myocardial fibrosis and use it to establish a compound screening system. In the Biowire II platform, cardiac tissues are suspended between a pair of poly(octamethylene maleate (anhydride) citrate) (POMaC) wires. Noninvasive functional readouts are realized on the basis of the deflection of the intrinsically fluorescent polymer. The disease model is constructed to recapitulate contractile, biomechanical, and electrophysiological complexities of fibrotic myocardium. Additionally, we constructed a heteropolar integrated model with fibrotic and healthy cardiac tissues coupled together. The integrated model captures the regional heterogeneity of scar lesion, border zone, and adjacent healthy myocardium. Finally, we demonstrate the utility of the system for the evaluation of antifibrotic compounds. The high-fidelity in vitro model system combined with convenient functional readouts could potentially facilitate the development of precision medicine strategies for cardiac fibrosis modeling and establish a pipeline for preclinical compound screening.

3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels

“…Many technologies are being developed, including self-assembled spheroids/organoids 6,[43][44][45] , organ-on-a-chip 46,47 , and microtissue platforms 41,42,48 . In addition, to better mimic cardiac disease, pathological features are being introduced using hypoxia-induced apoptosis 6 , mechanical stress 49 , or varied cardiac cell ratios 50 . Recent examples have also demonstrated how the introduction of electrical barriers such as holes in healthy cardiac tissue, or fibroblast dense regions can disrupt action potential propagation 45,51 .…”

(De)form and Function: Measuring Cellular Forces with Deformable Materials and Deformable Structures

“…The first‐generation Biowire is fabricated using soft lithography techniques in a manner similar to microposts with a piece of sterile surgical silk suture placed in the center channel of the PDMS . The second‐generation Biowire II platform consists of two elastomer‐based wires laid over a shallow chamber made of polystyrene ( Figure A,B) . Both Biowire and Biowire II are placed inside an electrical stimulation chamber to mature the heart cells …”

“…C) Cardiac tissue on a filamentous matrix. (A,B) Adapted under the terms of American Chemical Society AuthorChoice License . Copyright 2019, the Authors.…”

“…Furthermore, Biowire offers a high‐throughput, high‐content screening platform and has been used to investigate the effects of kinase inhibitors on cardiac tissue in addition to the side effects and cardiovascular risk of new drugs . The Biowire II platform uses the deflection of the wires to measure systolic and diastolic forces of cardiac tissue in real time . Biowire II has been used to monitor the progression of cardiac fibrosis at the interface of fibrotic and healthy tissue, while simultaneously functioning as a drug screening platform …”

“…The Biowire II platform uses the deflection of the wires to measure systolic and diastolic forces of cardiac tissue in real time . Biowire II has been used to monitor the progression of cardiac fibrosis at the interface of fibrotic and healthy tissue, while simultaneously functioning as a drug screening platform …”